Optical chemo- and biosensors based on integrated optical (bio)chemo-sensitive or (bio)chemo-functional waveguide grating structures permit the marking-free detection of (bio)molecular interactions in real time and are described in the literature (see e.g. U.S. Pat. Nos. 4,815,843 and 5,071,248). However marking detections are also possible (see e.g. WO 99/13320).
The method according to the invention not only represents a detection method, but also a separation technology since the substance to be tested or the substances to be tested, of the sample or of the matrix of samples, are separated in that the substance(s) binds(bind) onto the (bio)chemo-sensitive layer(s) located on the sensor chip.
A marking-free detection is effected in a first step, as is described in U.S. Pat. Nos. 4,815,843; 5,071,248; 5,738,825; 5,479,260 and EP 0,482,377. Subsequently, the substance (or parts (fragments) thereof) to be detected and binding onto the (bio)chemo-sensitive layer on the sensor chip is analysed more exactly in a mass spectrometer with a desorption step (and ionisation step).
The present invention describes detection systematics in which integrated optical chemo- and biosensorics (with or without marking technology (index marker, fluorescence marker, luminescence marker, phosphorescence marker, enzyme marker)) are combined with mass spectroscopy with a desorption step (and ionisation step). The desorption step releases the molecules from the surface of the sensor chip. The mass spectrometer measures the masses and/or the degree of ionisation of the molecules (atoms, ions, biomolecules, fragments etc.). The present invention thus creates detection systematics that further increases the detection sensitivity as well as the security of detection.